This invention relates to methods of producing quinoline derivatives and to compounds useful as intermediates in the production of 1,4-dihydro-4-oxo-quinoline-3-carboxylic acids.
It is known that certain 1,4-dihydro-4-oxo-quinoline-3-carboxylic acids exhibit antibacterial properties. For example, U.S. Pat. No. 4,017,622 discloses certain 7-piperazinyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives wherein the 1-position substituent is alkyl, benzyl or acetyl. U.S. Pat. No. 4,292,317 discloses certain 7-piperazinyl-6-halo-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives wherein the 1-position substituent is methyl, ethyl, vinyl or alkyl. In U.S. Pat. No. 4,284,629, various 4-oxo-1,4-dihydroquinoline-3-carboxylic acids are disclosed in which the 1-position substituent may be cycloalkyl, although corresponding derivatives containing a 7-piperazinyl substituent are not disclosed. The preparation of 1-ethyl-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid ethyl ester by reacting N-ethylaniline with ethoxymethylene-malonic acid diethyl ester followed by cyclization of the product in the presence of polyphosphoric acid ester at elevated temperature is described in J. Het. Chem. 12, 557 (1975).
It has now been discovered that 1,4-dihydro-4-oxo-quinoline-3-carboxylic acids can be produced by reacting an acetophenone with a dialkoxycarbonate to obtain the corresponding .beta.-ketoester, treating the .beta.-ketoester with a trialkylorthoformate in the presence of an acid anhydride followed by treatment with a substituted or unsubstituted amine to obtain the corresponding enaminoketoester, and reacting the enaminoketoester with a strong base to obtain the corresponding 1,4-dihydro-4-oxo-quinoline-3-carboxylic acid ester.